The Interconnected Genomic and Cerebral Evolution that Shaped Human Origins

这个研究小组正在进行一项全基因组范围的研究，以寻找人类祖先中有利的基因变化。重点是发现塑造人类庞大大脑和复杂认知能力的基因变化。发现方法的第一步是确定数千个编码蛋白质的基因，这些蛋白质在人类和其他卡他灵长类动物(如黑猩猩、大猩猩和恒河猴)的大脑皮层中发挥功能。接下来，对于这些大脑皮质表达的基因，确定哪些基因在表达模式上表现出物种差异，特别是识别那些表达模式在人类和其他卡他类动物之间不同的基因。最后，通过数据挖掘，不仅充分利用了人类基因组的完整DNA序列，而且还利用了即将完成的黑猩猩基因组和许多感兴趣的基因，以及来自一系列灵长类动物的不断增长的DNA序列数据。有了这个挖掘的序列，感兴趣的基因(大脑皮层细胞表达的那些基因)的数据通过系统发育分析确定了发生在基因调节区或蛋白质编码区的实际突变变化，这些变化是自然选择所青睐的。到目前为止获得的结果表明，基因调控和蛋白质编码这两种类型的突变改变塑造了人类表型的独特特征。通过结合遗传学家、生物化学家、神经学家和人类学家的大量专业知识，这项研究将架起不同学科的桥梁，以阐明人脑的基因-表型进化之间的关联，从而为寻求对人类起源的基本理解的研究做出贡献。这项研究应该具有广泛的社会影响。这将增加对人类扩大大脑的基因基础的理解。在这样做的过程中，它将识别那些在正向选择的力量下在较近的人类祖先中进化的编码蛋白质和DNA调控元件。这些信息在精神健康领域可能非常有价值，例如在为精神健康从业者寻找新的治疗剂方面。

This research team is conducting a genome-wide search for advantageous genetic changes in humankind's ancestry. A focus is on discovering the genetic changes that shaped humankind's enlarged brain and complex cognitive abilities. The first step in the method of discovery is to identify the many thousands of genes encoding proteins that function in the cerebral cortex of humans and other catarrhine primates such as chimpanzees, gorillas, and rhesus monkeys. Next, for these cerebral cortical brain expressed genes, determine which ones show species differences in expression patterns, especially identify those genes with expression patterns that differ between humans and the other catarrhines. Finally, by data mining take full advantage not only at the completed DNA sequence of the human genome but also of the soon to be completed chimpanzee genome and, for many of the genes of interest, the growing bodies of DNA sequence data from a range of primates. With this mined sequence, data for genes of interest (those that cerebral cortical cells express) identify by phylogenetic analysis the actual mutational changes that occurred either in gene regulatory regions or in protein encoding regions and that were favored by natural selection. Results obtained so far indicate that both types of mutational changes, gene regulatory and protein-encoding, shaped the distinctive features of the human phenotype. By combining the considerable expertise of geneticists, biochemists, neuroscientists, and anthropologists, this research will bridge diverse disciplines in order to elucidate the linked genotypic-phenotypic evolution of the human brain and thereby contribute to studies that seek a fundamental understanding of human origins.This research should have broad societal impact. It will increase understanding of the genetic underpinning of the enlarged brain humans have. In doing so, it will identify those encoded proteins and DNA regulatory elements that evolved in more recent human ancestry under the force of positive selection. This information could be of great value in the field of mental health such as in the search for new therapeutic agents for mental health practitioners.